Document Detail

Microglial cells induce cytotoxic effects toward colon carcinoma cells: measurement of tumor cytotoxicity with a gamma-glutamyl transpeptidase assay.
MedLine Citation:
PMID:  9009156     Owner:  NLM     Status:  MEDLINE    
Activated macrophages have been shown to exert cytostatic and cytotoxic effects toward tumor cells via nitric oxide (NO) release. In the CNS, microglial cells are considered to be the main resident population of immune effector cells. In this study, cytotoxic activity of N11, an immortalized murine microglial cell line, toward rat progressive DHD/PROb and regressive DHD/REGb colon carcinoma cells was examined in parallel with NO production. Cytotoxicity was evaluated using a novel method, the gamma-glutamyl transpeptidase (gamma-GTP) assay, based on the fact that DHD tumor cells expressed high levels of gamma-GTP activity, while no gamma-GTP activity was found in cells of the monocyte/macrophage lineage. Results showed that activation of N11 cells by interferon-gamma plus either lipopolysaccharide or tumor necrosis factor-alpha induced high amounts of NO release and cytotoxic effects toward DHD/PROb as well as DHD/REGb cells. NO release by activated N11 cells was augmented by addition of tumor cell-conditioned medium. Both NO release by N11 cells and cytotoxicity were blocked by addition of N(G)-monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, suggesting that cytotoxicity was mediated by N11-derived NO. However, in the presence of L-NMA an increased production of interleukin-6 was also observed. In conclusion, in opposition to information obtained with brain-derived endothelial cells, brain-derived microglial cells did not differentiate between progressive and regressive clones of colon carcinoma cells. Our results point to a specific role for both endothelial and microglial cell types in the context of brain metastasis. Microglial cells can be cytotoxic for tumor cells, and this cytotoxicity is mediated by NO.
J Murata; P Ricciardi-Castagnoli; P Dessous L'Eglise Mange; F Martin; L Juillerat-Jeanneret
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  70     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-02-20     Completed Date:  1997-02-20     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  169-74     Citation Subset:  IM    
Institute of Pathology, Lausanne, Switzerland.
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MeSH Terms
Biological Factors / pharmacology,  secretion
Biological Markers
Bone Marrow Cells
Brain Neoplasms / secondary
Carcinoma / pathology*,  secretion
Colonic Neoplasms / pathology*,  secretion
Culture Media, Conditioned / pharmacology
Cytotoxicity, Immunologic
Interferon-gamma, Recombinant / pharmacology
L Cells (Cell Line)
Lipopolysaccharides / pharmacology
Macrophages / physiology
Microglia / drug effects,  immunology*,  secretion
Neoplasm Proteins / analysis*,  antagonists & inhibitors
Nitric Oxide / biosynthesis
Nitric Oxide Synthase / antagonists & inhibitors
Rats, Inbred Lew
Recombinant Fusion Proteins / pharmacology
Tumor Markers, Biological / analysis*
Tumor Necrosis Factor-alpha / pharmacology
gamma-Glutamyltransferase / analysis*
omega-N-Methylarginine / pharmacology
Reg. No./Substance:
0/Biological Factors; 0/Biological Markers; 0/Culture Media, Conditioned; 0/Interferon-gamma, Recombinant; 0/Lipopolysaccharides; 0/Neoplasm Proteins; 0/Recombinant Fusion Proteins; 0/Tumor Markers, Biological; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; EC Oxide Synthase; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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